Overexpression Screen in Drosophila Identifies Neuronal Roles of GSK-3β/<i>shaggy</i>as a Regulator of AP-1-Dependent Developmental Plasticity

Franciscovich, Amy; Mortimer, A.J.; Freeman, Amanda; Gu, Jingsheng; Sanyal, Subhabrata

doi:10.1534/genetics.107.085555

Cited by 42 publications

(57 citation statements)

References 102 publications

(122 reference statements)

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“…The disruption of Armadillo (the Drosophila homolog of b-catenin) and Pangolin (the Drosophila homolog of TCF) has no significant effect on synaptic phenotypes (Miech et al, 2008), which suggests a limited role of the canonical Armadillo/Pangolin-dependent pathway in this process. Instead, the actions of Fz are probably mediated by the inhibition of Shaggy (the Drosophila homolog of Gsk3b), a substrate of which is Futsch [the Drosophila ortholog of microtubule associated protein 1B (MAP1B)] (Franciscovich et al, 2008;Franco et al, 2004;Gogel et al, 2006;Roos et al, 2000) (Fig. 4A).…”

Section: Wnts In the Invertebrate Nmjmentioning

confidence: 99%

To build a synapse: signaling pathways in neuromuscular junction assembly

2010

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SummarySynapses, as fundamental units of the neural circuitry, enable complex behaviors. The neuromuscular junction (NMJ) is a synapse type that forms between motoneurons and skeletal muscle fibers and that exhibits a high degree of subcellular specialization. Aided by genetic techniques and suitable animal models, studies in the past decade have brought significant progress in identifying NMJ components and assembly mechanisms. This review highlights recent advances in the study of NMJ development, focusing on signaling pathways that are activated by diffusible cues, which shed light on synaptogenesis in the brain and contribute to a better understanding of muscular dystrophy. Key words: Neural development, Neuromuscular junction, Retrograde signaling, Synapse formation IntroductionThe brain contains billions of nerve cells, or neurons, which receive and integrate signals from the environment, and which govern the body's responses. Nervous system activity is made possible by synapses, contacts formed either between neurons or between a neuron and a target cell. Synapses are asymmetric structures in which neurotransmitter molecules are released from the presynaptic membrane and activate receptors on the postsynaptic membrane, thus establishing neuronal communication. As such, synapses are fundamental units of neural circuitry and enable complex behaviors. The neuromuscular junction (NMJ) is a type of synapse formed between motoneurons and skeletal muscle fibers. Large and easily accessed experimentally, this peripheral synapse has contributed greatly to the understanding of the general principles of synaptogenesis and to the development of potential therapeutic strategies for muscular disorders. The NMJ uses different neurotransmitters in different species; for example, acetylcholine (ACh) in vertebrates and glutamate in Drosophila, both of which are excitatory and cause muscle contraction. In Caenorhabditis elegans, there are two types of NMJs: at excitatory NMJs, ACh causes muscle contraction, whereas inhibitory NMJs release g-aminobutyric acid (GABA) to cause muscle relaxation. Motor nerve terminals differentiate to form presynaptic active zones, where synaptic vesicles dock and release neurotransmitters. On the apposed postsynaptic membranes, neurotransmitter receptors are packed at high densities. Aided by genetic techniques and by the use of suitable animal models, including rodents, zebrafish, Drosophila and C. elegans, studies in the past decade have brought significant progress, not only in identifying components present in pre-and postsynaptic membranes, but also in understanding the mechanisms that underpin NMJ assembly. This review highlights recent advances in the study of NMJ development, focusing on signaling pathways that are activated by diffusible cues from motor nerves and muscle fibers. Readers are referred to other outstanding reviews for a broad view of NMJ development (see Froehner, 1993;Hall and Sanes, 1993;Kummer et al., 2006;Salpeter and Loring, 1985;Schaeffer et al., 2001). NMJ formati...

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Section: Wnts In the Invertebrate Nmjmentioning

confidence: 99%

To build a synapse: signaling pathways in neuromuscular junction assembly

2010

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“…The Cha-GAL80 transgene was included to inhibit expression in non-identified cholinergic sensory neurons and interneurons. UAS-fos; UAS-jun and UAS-Jbz strains have been described previously (Eresh et al, 1997;Sanyal et al, 2002;Franciscovich et al, 2008). The w;; kayak-GAL4, UAS-nls-GFP was used as a reporter for fos (Freeman et al, 2010).…”

Section: Animalsmentioning

confidence: 99%

Temporal coherency between receptor expression, neural activity and AP-1-dependent transcription regulatesDrosophilamotoneuron dendrite development

et al. 2013

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SUMMARYNeural activity has profound effects on the development of dendritic structure. Mechanisms that link neural activity to nuclear gene expression include activity-regulated factors, such as CREB, Crest or Mef2, as well as activity-regulated immediate-early genes, such as fos and jun. This study investigates the role of the transcriptional regulator AP-1, a Fos-Jun heterodimer, in activity-dependent dendritic structure development. We combine genetic manipulation, imaging and quantitative dendritic architecture analysis in a Drosophila single neuron model, the individually identified motoneuron MN5. First, D7 nicotinic acetylcholine receptors (nAChRs) and AP-1 are required for normal MN5 dendritic growth. Second, AP-1 functions downstream of activity during MN5 dendritic growth. Third, using a newly engineered AP-1 reporter we demonstrate that AP-1 transcriptional activity is downstream of D7 nAChRs and Calcium/calmodulin-dependent protein kinase II (CaMKII) signaling. Fourth, AP-1 can have opposite effects on dendritic development, depending on the timing of activation. Enhancing excitability or AP-1 activity after MN5 cholinergic synapses and primary dendrites have formed causes dendritic branching, whereas premature AP-1 expression or induced activity prior to excitatory synapse formation disrupts dendritic growth. Finally, AP-1 transcriptional activity and dendritic growth are affected by MN5 firing only during development but not in the adult. Our results highlight the importance of timing in the growth and plasticity of neuronal dendrites by defining a developmental period of activity-dependent AP-1 induction that is temporally locked to cholinergic synapse formation and dendritic refinement, thus significantly refining prior models derived from chronic expression studies.

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“…Indeed, many components of the JNK signaling pathway have been uncovered in modifier screens aimed at identifying suppressors of eye defects caused by protein overexpression (Wang et al 2005; Franciscovich et al 2008). Since overexpressing proteins often leads to non-specific cell death, and since CC/PPC cell death is readily detected as “glassy” eyes by light microscopy, the eye has been frequently used for such misexpression studies.…”

Section: Drosophila Lens Specificationmentioning

confidence: 99%

The lens in focus: a comparison of lens development in Drosophila and vertebrates

2011

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The evolution of the eye has been a major subject of study dating back centuries. The advent of molecular genetics offered the surprising finding that morphologically distinct eyes rely on conserved regulatory gene networks for their formation. While many of these advances often stemmed from studies of the compound eye of the fruit fly, Drosophila melanogaster, and later translated to discoveries in vertebrate systems, studies on vertebrate lens development far outnumber those in Drosophila. This may be largely historical, since Spemann and Mangold’s paradigm of tissue induction was discovered in the amphibian lens. Recent studies on lens development in Drosophila have begun to define molecular commonalities with the vertebrate lens. Here, we provide an overview of Drosophila lens development, discussing intrinsic and extrinsic factors controlling lens cell specification and differentiation. We then summarize key morphological and molecular events in vertebrate lens development, emphasizing regulatory factors and networks strongly associated with both systems. Finally, we provide a comparative analysis that highlights areas of research that would help further clarify the degree of conservation between the formation of dioptric systems in invertebrates and vertebrates.

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Overexpression Screen in Drosophila Identifies Neuronal Roles of GSK-3β/shaggyas a Regulator of AP-1-Dependent Developmental Plasticity

Cited by 42 publications

References 102 publications

To build a synapse: signaling pathways in neuromuscular junction assembly

To build a synapse: signaling pathways in neuromuscular junction assembly

Temporal coherency between receptor expression, neural activity and AP-1-dependent transcription regulatesDrosophilamotoneuron dendrite development

The lens in focus: a comparison of lens development in Drosophila and vertebrates

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